{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:10:34Z","timestamp":1793157034213,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In 2016 a new syndrome with postnatal short stature and low IGF1 bioavailability caused by biallelic loss\u2010of\u2010function mutations in the gene encoding the metalloproteinase pregnancy\u2010associated plasma protein A2 (PAPP\u2010A2) was described in two families. Here we report two siblings of a third family from Saudi Arabia with postnatal growth retardation and decreased IGF1 availability due to a new homozygous nonsense mutation (p.Glu886* in exon 7) in\n                    <jats:italic>PAPPA2<\/jats:italic>\n                    . The two affected males showed progressively severe short stature starting around 8\u2009years of age, moderate microcephaly, decreased bone mineral density, and high circulating levels of total IGF1, IGFBP3, and the IGF acid\u2010labile subunit (IGFALS), with decreased free IGF1 concentrations. Interestingly, circulating IGF2 and IGFBP5 were not increased. An increase in growth velocity and height was seen in the prepuberal patient in response to rhIGF1. These patients contribute to the confirmation of the clinical picture associated with PAPP\u2010A2 deficiency and that the\n                    <jats:italic>PAPPA2<\/jats:italic>\n                    gene should be studied in all patients with short stature with this characteristic phenotype. Hence, pediatric endocrinologists should measure circulating PAPP\u2010A2 levels in the study of short stature as very low or undetectable levels of this protein can help to focus the diagnosis and treatment.\n                  <\/jats:p>","DOI":"10.1111\/cge.14030","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T03:39:35Z","timestamp":1626493175000},"page":"601-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Short stature with low insulin\u2010like growth factor 1 availability due to pregnancy\u2010associated plasma protein\n                    <scp>A2<\/scp>\n                    deficiency in a Saudi family"],"prefix":"10.1111","volume":"100","author":[{"given":"Amir","family":"Babiker","sequence":"first","affiliation":[{"name":"King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"College of Medicine, King Saud bin Abdul\u2010Aziz University for Health Sciences Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"King Abdullah International Medical Research Center Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Al Noaim","sequence":"additional","affiliation":[{"name":"King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"Department of Pediatrics, College of Medicine King Faisal University  Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al Swaid","sequence":"additional","affiliation":[{"name":"King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"College of Medicine, King Saud bin Abdul\u2010Aziz University for Health Sciences Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"King Abdullah International Medical Research Center Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Alfadhel","sequence":"additional","affiliation":[{"name":"King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"College of Medicine, King Saud bin Abdul\u2010Aziz University for Health Sciences Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"King Abdullah International Medical Research Center Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Deeb","sequence":"additional","affiliation":[{"name":"Pediatric Endocrine Division, Sheikh Shakhbout Medical City Abu Dhabi &amp; Khalifa University  Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mart\u00edn\u2010Rivada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Barrios","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa Universidad Aut\u00f3noma de Madrid  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Fisiopatolog\u00eda de la Obesidad y Nutrici\u03ccn (CIBEROBN) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"P\u00e9rez\u2010Jurado","sequence":"additional","affiliation":[{"name":"Genetics Unit, Department of Experimental and Health Sciences Universitat Pompeu Fabra  Barcelona Spain"},{"name":"Service of Genetics Hospital del Mar and Hospital del Mar Research Institute (IMIM)  Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alfares","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"Departement of Laboratory and Pathology Medicine King Abdullah International Medical Research Center  Riyadh Saudi Arabia"},{"name":"Departement of Pediatrics, College of Medicine Qassim University  Buraidah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Al Alwan","sequence":"additional","affiliation":[{"name":"King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"College of Medicine, King Saud bin Abdul\u2010Aziz University for Health Sciences Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"},{"name":"King Abdullah International Medical Research Center Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0276","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa Universidad Aut\u00f3noma de Madrid  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Fisiopatolog\u00eda de la Obesidad y Nutrici\u03ccn (CIBEROBN) Instituto de Salud Carlos III  Madrid Spain"},{"name":"IMDEA. Food Institute CEIUAM+CSI  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201707950"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2018.05.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201506106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-17-0298"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2751"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-015-0108-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486336"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01411"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09410"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000502231"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2018.04.001"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14030","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14030","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:26:53Z","timestamp":1741735613000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/cge.14030"],"URL":"https:\/\/doi.org\/10.1111\/cge.14030","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14030\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14030\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14030\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14030\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14030\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14030\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"assertion":[{"value":"2021-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}